Advertisement
Amendment history:

ResearchIn-Press PreviewBone biology Open Access | 10.1172/jci.insight.165604

Mitochondrial B-oxidation of adipose-derived fatty acids by osteoblast fuels parathyroid hormone-induced bone formation

Nathalie Alekos,1 Priyanka Kushwaha,2 Soohyun Kim,3 Zhu Li,1 Abdullah Abood,4 Naomi Dirckx,1 Susan Aja,5 Joe Kodama,1 Jean Garcia-Diaz,1 Satoru Otsuru,1 Elizabeth Rendina-Ruedy,6 Michael J. Wolfgang,7 and Ryan C. Riddle1

1Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, United States of America

2Division of Rheumatology, Inflammation, and Immunity, Department of Medicin, Brigham and Women’s Hospital, Boston, United States of America

3Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

4Center for Public Health Genomics, University of Virgina, Charlottesville, United States of America

5Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Department of Medicine and Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, United States of America

7Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, United States of America

Find articles by Alekos, N. in: PubMed | Google Scholar

1Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, United States of America

2Division of Rheumatology, Inflammation, and Immunity, Department of Medicin, Brigham and Women’s Hospital, Boston, United States of America

3Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

4Center for Public Health Genomics, University of Virgina, Charlottesville, United States of America

5Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Department of Medicine and Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, United States of America

7Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, United States of America

Find articles by Kushwaha, P. in: PubMed | Google Scholar

1Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, United States of America

2Division of Rheumatology, Inflammation, and Immunity, Department of Medicin, Brigham and Women’s Hospital, Boston, United States of America

3Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

4Center for Public Health Genomics, University of Virgina, Charlottesville, United States of America

5Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Department of Medicine and Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, United States of America

7Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, United States of America

Find articles by Kim, S. in: PubMed | Google Scholar

1Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, United States of America

2Division of Rheumatology, Inflammation, and Immunity, Department of Medicin, Brigham and Women’s Hospital, Boston, United States of America

3Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

4Center for Public Health Genomics, University of Virgina, Charlottesville, United States of America

5Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Department of Medicine and Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, United States of America

7Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, United States of America

Find articles by Li, Z. in: PubMed | Google Scholar

1Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, United States of America

2Division of Rheumatology, Inflammation, and Immunity, Department of Medicin, Brigham and Women’s Hospital, Boston, United States of America

3Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

4Center for Public Health Genomics, University of Virgina, Charlottesville, United States of America

5Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Department of Medicine and Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, United States of America

7Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, United States of America

Find articles by Abood, A. in: PubMed | Google Scholar |

1Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, United States of America

2Division of Rheumatology, Inflammation, and Immunity, Department of Medicin, Brigham and Women’s Hospital, Boston, United States of America

3Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

4Center for Public Health Genomics, University of Virgina, Charlottesville, United States of America

5Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Department of Medicine and Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, United States of America

7Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, United States of America

Find articles by Dirckx, N. in: PubMed | Google Scholar

1Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, United States of America

2Division of Rheumatology, Inflammation, and Immunity, Department of Medicin, Brigham and Women’s Hospital, Boston, United States of America

3Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

4Center for Public Health Genomics, University of Virgina, Charlottesville, United States of America

5Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Department of Medicine and Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, United States of America

7Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, United States of America

Find articles by Aja, S. in: PubMed | Google Scholar

1Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, United States of America

2Division of Rheumatology, Inflammation, and Immunity, Department of Medicin, Brigham and Women’s Hospital, Boston, United States of America

3Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

4Center for Public Health Genomics, University of Virgina, Charlottesville, United States of America

5Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Department of Medicine and Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, United States of America

7Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, United States of America

Find articles by Kodama, J. in: PubMed | Google Scholar

1Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, United States of America

2Division of Rheumatology, Inflammation, and Immunity, Department of Medicin, Brigham and Women’s Hospital, Boston, United States of America

3Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

4Center for Public Health Genomics, University of Virgina, Charlottesville, United States of America

5Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Department of Medicine and Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, United States of America

7Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, United States of America

Find articles by Garcia-Diaz, J. in: PubMed | Google Scholar

1Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, United States of America

2Division of Rheumatology, Inflammation, and Immunity, Department of Medicin, Brigham and Women’s Hospital, Boston, United States of America

3Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

4Center for Public Health Genomics, University of Virgina, Charlottesville, United States of America

5Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Department of Medicine and Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, United States of America

7Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, United States of America

Find articles by Otsuru, S. in: PubMed | Google Scholar |

1Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, United States of America

2Division of Rheumatology, Inflammation, and Immunity, Department of Medicin, Brigham and Women’s Hospital, Boston, United States of America

3Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

4Center for Public Health Genomics, University of Virgina, Charlottesville, United States of America

5Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Department of Medicine and Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, United States of America

7Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, United States of America

Find articles by Rendina-Ruedy, E. in: PubMed | Google Scholar

1Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, United States of America

2Division of Rheumatology, Inflammation, and Immunity, Department of Medicin, Brigham and Women’s Hospital, Boston, United States of America

3Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

4Center for Public Health Genomics, University of Virgina, Charlottesville, United States of America

5Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Department of Medicine and Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, United States of America

7Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, United States of America

Find articles by Wolfgang, M. in: PubMed | Google Scholar

1Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, United States of America

2Division of Rheumatology, Inflammation, and Immunity, Department of Medicin, Brigham and Women’s Hospital, Boston, United States of America

3Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

4Center for Public Health Genomics, University of Virgina, Charlottesville, United States of America

5Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Department of Medicine and Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, United States of America

7Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, United States of America

Find articles by Riddle, R. in: PubMed | Google Scholar |

Published February 2, 2023 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.165604.
Copyright © 2023, Alekos et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published February 2, 2023 - Version history
View PDF
Abstract

The energetic costs of bone formation require osteoblasts to coordinate their activities with tissues, like adipose, that can supply energy-dense macronutrients. In the case of intermittent parathyroid hormone treatment (PTH), a strategy used to reduce fracture risk, bone formation is proceeded by a change in systemic lipid homeostasis. To investigate the requirement for fatty acid oxidation by osteoblasts during PTH-induced bone formation, we subjected mice with osteoblast-specific deficiency of mitochondrial long-chain β-oxidation as well as mice with adipocyte-specific deficiency for the PTH receptor or adipose triglyceride lipase to an anabolic treatment regime. PTH increased the release of fatty acids from adipocytes and B-oxidation by osteoblasts, while the genetic mouse models were resistant to the hormone’s anabolic effect. Collectively, these data suggest that PTH’s anabolic actions requires coordinated signaling between bone and adipose, wherein a lipolytic response liberates fatty acids that are oxidized by osteoblasts to fuel bone formation

Graphical Abstract
graphical abstract
Version history
  • Version 1 (February 2, 2023): In-Press Preview
  • Version 2 (March 22, 2023): Electronic publication
  • Version 3 (September 23, 2025): In Figure 6D, the Ad∆Atgl panel was corrected (it was inadvertently duplicated from the control panel in the initial version)
Advertisement
Advertisement